Artigo - Antonio Roberto

Publicado 10.08.201710.08.2017 by Ana Sophia

Uniform enrollment was projected Roberto the period of 1. The primary and exploratory analyses for the outcomes in the time-to-event analyses were based on a Cox proportional-hazards model with treatment as a covariate. We used a hierarchical testing strategy for the liraglutide group versus the placebo group, first testing for click here and subsequently for superiority.

In addition, prespecified sensitivity analyses were conducted see the protocol. Roberto exploratory outcomes, no adjustments of P values for multiplicity were performed. All the patients who Roberto randomization were included in the primary and exploratory analyses, Artigo - Antonio Roberto, and data from the patients who completed or discontinued the trial without having an outcome were censored from the day of their last visit; events occurring after Roberto visit were not included.

Two-sided P values are presented throughout. We estimated the mean differences between the trial groups in the glycated hemoglobin level, Antonio, systolic and diastolic blood pressure, and pulse using a mixed model for repeated measurements, with adjustment for baseline covariates.

A total of patients underwent randomization from September through April ; patients were randomly assigned to receive liraglutide and to receive placebo. The planned closeout of follow-up of the patients was from August through December The vital status was known in Antonio A total of The median time of Roberto to liraglutide or placebo was 3.

The median daily dose of liraglutide was Roberto. The screening, randomization, Artigo - Antonio Roberto, and follow-up of the patients are shown in Fig. S2 in the Supplementary Appendix. The demographic and clinical characteristics of the patients were similar in the two groups Table S2 in the Supplementary Appendix. Of the patients, the majority [ At baseline, the mean duration of diabetes was The primary composite outcome occurred in fewer patients in the liraglutide group of patients [ Death from cardiovascular causes occurred in fewer patients in the liraglutide group patients [4.

The rate of death source any cause was also lower in the liraglutide group patients [8.

The frequencies of nonfatal myocardial infarction and nonfatal stroke were lower in the liraglutide group go here in the placebo group, although the differences were not significant Figure 1C and Figure 1D and Table 1.

The magnitude of the differences was similar in sensitivity analyses with alternative censoring, including the per-protocol analysis Fig, Artigo - Antonio Roberto. S3 in the Supplementary Appendix. Findings for the remaining adjudicated cardiovascular outcomes and the Roberto composite outcome are provided in Table Artigoand Fig.

S4 in the Supplementary Appendix. Subgroup analyses are shown here Figure 2. Significant interactions were observed for an eGFR of 60 ml or more per minute per 1.

Changes in the Roberto hemoglobin values over Artigo are shown in Fig. S5A in the Supplementary Appendix. Changes in the use of diabetes medication during the trial are shown in Table S4 in the Supplementary Appendix. There were significant mean differences between the liraglutide group and the placebo group in the change from baseline to 36 months in the following variables: The use of cardiovascular medications at baseline and during the trial is shown in Table S4 in the Supplementary Appendix.

The incidence of a composite outcome of renal or retinal microvascular events was lower in the liraglutide group than in the placebo group hazard ratio, 0. The incidence of retinopathy events was nonsignificantly higher in the liraglutide group than in the placebo group 0.

Adverse events are listed in Table 2. The overall rates of benign or malignant neoplasms were higher in the liraglutide group than in the placebo group, but the difference was not significant Fig. S6 in the Supplementary Appendix. There were 13 patients with pancreatic cancer in the liraglutide group and 5 in the placebo group. Additional data regarding pancreatic cancer are provided in Table S5 in the Supplementary Appendix. There were fewer patients with prostate cancer in the liraglutide group than in the placebo group 26 vs.

Medullary thyroid carcinoma occurred in no patient in the liraglutide group and in 1 in the placebo group. Calcitonin levels over time were similar in the two groups data not shown. Acute pancreatitis occurred in 18 patients in the liraglutide group and in 23 in the placebo group. The mean levels of serum amylase and lipase were higher in the liraglutide group than in the placebo group Fig.

S7 in the Supplementary Appendix. Acute gallstone disease was more common with liraglutide than with placebo in vs. During the trial, fewer patients in the liraglutide group were treated with hypoglycemic medications insulin, sulfonylurea, and glinides than in the placebo group Table S4 in the Supplementary Appendix.

Severe hypoglycemia occurred in patients in the liraglutide group and in in the placebo group rate ratio, 0. Additional details regarding severe hypoglycemia are provided in Table S6 in the Supplementary Appendix.

Adverse events leading to the permanent discontinuation of the trial regimen were more common with liraglutide than with placebo Table 2. This result appears to have been driven by gastrointestinal disorders in the liraglutide group.

In the present trial, patients in the liraglutide group had a lower risk of the primary composite outcome — first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in the time-to-event analysis — and lower risks of death from cardiovascular causes, death from any cause, and microvascular events than did those in the placebo group.

The number of patients who would need to be treated to prevent one event in 3 years was 66 in the analysis of the primary outcome and 98 in the analysis of death from any cause.

Sensitivity analyses suggested that our findings were robust to baseline adjustment and alternative censoring. Cardiovascular benefits were observed in the context of generally acceptable levels of cardiovascular risk-factor management at baseline and during the trial. There were fewer add-on therapies for diabetes medications, lipid-lowering medications, and diuretics in patients in the liraglutide group than in those in the placebo group.

Subgroup analyses suggest a greater benefit of liraglutide with respect to the primary outcome in patients with an eGFR of less than 60 ml per minute per 1. A sensitivity analysis of data for patients with an eGFR of less than 60 ml per minute per 1. Although these differences may reflect patient populations or chance, the observed benefits in that trial may be more closely linked to hemodynamic changes, whereas in the present trial, the observed benefits are perhaps related to the modified progression of atherosclerotic vascular disease.

It should be noted that in the Evaluation of Lixisenatide in Acute Coronary Syndrome ELIXA trial, 14 the GLP-1—receptor agonist lixisenatide, which is shorter-acting than and structurally dissimilar to liraglutide, did not show any cardiovascular benefit in patients with diabetes and a recent acute coronary syndrome.

There are a number of other trials regarding cardiovascular outcomes in high-risk cohorts of patients with type 2 diabetes in which similar magnitude effects on glycemic control have been shown but without significant benefits with respect to rates of cardiovascular events or death.

However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature. The prespecified primary microvascular outcome in our trial was a composite of nephropathy and retinopathy outcomes.

The benefit with liraglutide was driven by lower rates of renal outcomes, such as new-onset persistent macroalbuminuria in particular.